Linked Life Data

20800070

Source:http://linkedlifedata.com/resource/pubmed/id/20800070

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-10-4
pubmed:databankReference
pubmed:abstractText
Recombinant expression systems differ in the type of glycosylation they impart on expressed antigens such as the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, potentially affecting their biological properties. We performed head-to-head antigenic, immunogenic and molecular profiling of two distantly related Env surface (gp120) antigens produced in different systems: (a) mammalian (293 FreeStyle cells; 293F) cells in the presence of kifunensine, which impart only high-mannose glycans; (b) insect cells (Spodoptera frugiperda, Sf9), which confer mainly paucimannosidic glycans; (c) Sf9 cells recombinant for mammalian glycosylation enzymes (Sf9 Mimic), which impart high-mannose, hybrid and complex glycans without sialic acid; and (d) 293F cells, which impart high-mannose, hybrid and complex glycans with sialic acid. Molecular models revealed a significant difference in gp120 glycan coverage between the Sf9-derived and wild-type mammalian-cell-derived material that is predicted to affect ligand binding sites proximal to glycans. Modeling of solvent-exposed surface electrostatic potentials showed that sialic acid imparts a significant negative surface charge that may influence gp120 antigenicity and immunogenicity. Gp120 expressed in systems that do not incorporate sialic acid displayed increased ligand binding to the CD4 binding and CD4-induced sites compared to those expressed in the system that do, and imparted other more subtle differences in antigenicity in a gp120 subtype-specific manner. Non-sialic-acid-containing gp120 was significantly more immunogenic than the sialylated version when administered in two different adjuvants, and induced higher titers of antibodies competing for CD4 binding site ligand-gp120 interaction. These findings suggest that non-sialic-acid-imparting systems yield gp120 immunogens with modified antigenic and immunogenic properties, considerations that should be considered when selecting expression systems for glycosylated antigens to be used for structure-function studies and for vaccine use.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
403
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-47
pubmed:dateRevised
2011-10-17
pubmed:meshHeading
pubmed-meshheading:20800070-Animals, pubmed-meshheading:20800070-Antigens, CD4, pubmed-meshheading:20800070-Antigens, Viral, pubmed-meshheading:20800070-Cell Culture Techniques, pubmed-meshheading:20800070-Cell Line, pubmed-meshheading:20800070-Genetic Vectors, pubmed-meshheading:20800070-Glycoproteins, pubmed-meshheading:20800070-Glycosylation, pubmed-meshheading:20800070-HIV Antibodies, pubmed-meshheading:20800070-HIV Envelope Protein gp120, pubmed-meshheading:20800070-HIV-1, pubmed-meshheading:20800070-Humans, pubmed-meshheading:20800070-Immunoglobulin G, pubmed-meshheading:20800070-Mice, pubmed-meshheading:20800070-Mice, Inbred BALB C, pubmed-meshheading:20800070-Models, Molecular, pubmed-meshheading:20800070-Molecular Sequence Data, pubmed-meshheading:20800070-Polysaccharides, pubmed-meshheading:20800070-Protein Binding, pubmed-meshheading:20800070-Protein Structure, Tertiary, pubmed-meshheading:20800070-Recombinant Proteins, pubmed-meshheading:20800070-Sequence Analysis, DNA, pubmed-meshheading:20800070-Spodoptera, pubmed-meshheading:20800070-Static Electricity
pubmed:year
2010
pubmed:articleTitle
Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity.
pubmed:affiliation
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't